Microchip processing method and apparatus

ABSTRACT

The processing apparatus for microchips, each at least having a main flow path performing migration of a sample for analysis inside a sheet-like member, comprises a holding part holding microchips so that the multiple main flow paths are provided; a pretreatment part common to the multiple main flow paths for performing a pretreatment step prior to an analysis step in each of the multiple main flow paths; a processing part for performing analysis in each of the main flow paths independently of the others; and a control part controlling an operation in the pretreatment part so that when a pretreatment step for one main flow path ends, a pretreatment for a next main flow path starts and further controlling an operation in the processing part so that an analysis is subsequently performed for the main flow path where the pretreatment step has ended.

This application is a divisional application of application Ser. No.11/041,425, filed on Jan. 25, 2005, now U.S. Pat. No. 7,678,254 B2,which is based on Priority Document JP 2004-019685, filed on Jan. 28,2004, the entire contents of which are hereby incorporated by reference.

FIELD OF THE INVENTION

This invention relates to a microchip processing method and an apparatusthereof performing analysis of those such as a microchip electrophoreticmethod, a micro-liquid chromatography and the like.

BACKGROUND ART

Microchip electrophoresis employs a microchip having an electrophoreticflow path including a separation flow path formed inside a sheet-likemember. A sample such as DNA, RNA or protein introduced into one end ofa separation flow path is electrophoresed in a direction toward theother end of the separation flow path for separation by a voltageapplied between both ends of the separation flow path, followed bydetection.

In microchip electrophoresis, an apparatus has been developed thatrepeatedly uses a single microchip having a single electrophoretic flowpath to thereby automatically perform filling of a buffer solution,injection of a sample, and detection of electrophoresed/separated samplecomponents (see JP-A No. 10-246721).

In order to raise a throughput in analysis, electrophoretic apparatuseshave also been proposed, each of which employs a microchip provided withmultiple flow paths. An example of such apparatuses is one which employsa single microchip provided with twelve sample introduction flow pathsand one separation flow path. In the example apparatus, after filling ofa separation buffer solution into the flow paths, dispensation ofsamples are manually performed on all of the sample introduction flowpaths, and thereafter electrophoresis is sequentially performed in theseparation flow path to separate the samples into components thereof andto thereby obtain data (see Bunseki, No. 5, pp. 267 to 270 (2002)).

In another apparatus, a single cartridge is provided with twelve flowpaths constituted of capillaries in which filling of a separation buffersolution, dispensation of samples, separation by electrophoresis andacquisition of data are performed automatically (Electrophoresis, 2003,24, pp. 93 to 95).

In a micro-liquid chromatography, a microchip has been provided with aliquid flow path including a separation column, and a sample introducedinto one end of the separation column is migrated in a direction towardthe other end of the separation column to thereby separate the sampleinto components, followed by analyzing the components (see Anal. Chem.,70, p. 3790 (1998)).

The above apparatuses described in the journals “Bunseki” and“Electrophoresis” are useful in terms of throughput. However, bothapparatuses in the examples are operated only under limitations that anoperation is based on a batch processing and the same separation buffersolution is used on twelve samples, on all of which analysis has to beperformed in the same condition. That is, it is impossible to employ adifferent separation buffer solution on each sample and to individuallyset conditions for electrophoresis on respective samples.

In a case where the number of samples is less than 12, one or moreelectrophoretic flow paths are wastefully not used, leading to costincreasing.

The same problem can be seen in liquid chromatography.

SUMMARY OF THE INVENTION

It is an object of the present invention to enable analysis conditionssuch as separation buffer solutions or electrophoretic conditions forelectrophoresis and mobile phases or liquid feeding conditions forliquid chromatography to be set for each sample as well as to raise aseparation throughput in electrophoresis or liquid chromatography.

The invention is directed to a processing method in which a microchipprovided with at least a main flow path performing migration of a samplesolution for analysis inside a sheet-like member is employed, includinga pretreatment step prior to the analysis step for the main flow path.The pretreatment steps are performed using a dispenser common to themultiple main flow paths and are performed such that when a pretreatmentfor one main flow path ends, a pretreatment for the next main flow pathstarts. Each of the analysis steps, subsequent to the pretreatment, isperformed in a corresponding main flow path independently of the others,and the analysis steps are performed simultaneously to one another inthe multiple main flow paths.

The term “analysis” includes, in its meaning, electrophoretic separationand detection in microchip eletrophoresis; separation, elution anddetection in column in liquid chromatography; and reaction and detectionof a reaction product in a reaction apparatus.

An example of such a microchip processing method is a microchipelectrophoretic method. In its case, the microchip is provided with anelectrophoretic flow path including a separation flow path as a mainflow path, and the analysis step is a step of electrophoresing a sampleintroduced at one end of the separation flow path in the separation flowpath in a direction toward the other end thereof due to a voltageapplied between both ends of the separation path to thereby separate thesample into components thereof and to detect the components, while thepretreatment step includes at least filling of a separation buffersolution and injection of the sample into the electrophoretic flow path.

The electrophoresis step as the analysis step in the microchipelectrophoretic method includes electrophoretic separation anddetection. The electrophoretic separation includes zone electrophoresisand separation in the presence of a separation polymer or gel. Detectionincludes optical detection, electrochemical detection or the like. Theoptical detection may be fluorometric measurement measuring fluorescenceemitted from a sample by irradiating a separated component thereof withexcitation light, absorption measurement measuring an absorbance ofmeasurement light by causing the light to pass through a sample, ormeasurement of chemiluminescence or bioluminescence from a separatedcomponent of a sample.

The pretreatment may include addition of a size marker, a fluorescentreagent or the like.

In a case where a different sample has been processed in advance in anelectrophoretic flow path that is to then be filled with a separationbuffer solution, the pretreatment step may include a step of cleaningthe electrophoretic flow path with the separation buffer solution priorto filling of the separation buffer solution.

The electrophoretic flow path may be constituted of either only aseparation flow path or a flow path of a cross-injection scheme in whicha sample introducing flow path intersects with the separation flow path.In a case where the flow path is of the cross-injection scheme, theelectrophoresis step includes a step of feeding a sample introduced atone end of the sample introducing flow path to an intersection of thesample introducing flow path and the separation flow path, and a step ofseparating the sample fed to the intersection in the separation flowpath to detect components thereof.

Another example of such a microchip processing method is of liquidchromatography. In its case, a microchip is provided with a liquid feedflow path including a separation column as a main flow path, and theanalysis step is a liquid chromatography step of moving a sampleintroduced at one end of the separation column in a direction toward theother end thereof to thereby separate the sample into components thereofand to detect the components and the pretreatment step includes at leastinjection of the sample into the separation column.

The liquid chromatography step includes separation/elution anddetection. The separation/elution includes separation and elution in anopen tube column or a packed column, and the packed column also includesa nanostructure such as a pillar. Further, the elution includes agradient elution in which a mobile phase is changed in composition withtime.

Detection in liquid chromatography includes an optical detection, anelectrochemical detection and the like. The optical detection may befluorometric measurement measuring fluorescence emitted from a sample byirradiating a separated component thereof with excitation light,absorption measurement measuring an absorbance of measurement light bycausing the light to pass through a sample, or measurement ofchemiluminescence or bioluminescence from a separated component of asample.

The invention is to repeatedly use a flow path formed in a microchip.The multiple flow paths in which processing is performed in theinvention may be formed either in a single substrate or in multiplesubstrates in a separate state. Only one main flow path may be providedin a microchip because of ease in handling, in which case microchips innumber equal to the number of main flow paths are arranged to performprocessing.

A microchip processing apparatus of the invention is a processingapparatus provided with microchips each at least having a main flow pathperforming migration of a sample solution for analysis inside asheet-like member, includes a holding part holding microchips so thatthe multiple main flow paths are provided; a pretreatment part common tothe multiple main flow paths for performing a pretreatment step prior toan analysis step in each of the multiple main flow paths; a processingpart for performing analysis in each of the main flow pathsindependently of the others; and a control part controlling an operationin the pretreatment step so that when the pretreatment step in one mainflow path ends, the process moves to a pretreatment step in the nextmain flow path and further controlling an operation in the processingpart so that the analysis is subsequently performed in the main flowpath where the pretreatment step has ended.

This microchip processing apparatus includes a microchip electrophoreticapparatus and a microchip liquid chromatograph.

In a case where the microchip processing apparatus is realized as amicrochip electrophoretic apparatus, each of the microchips has anelectrophoretic flow path including a separation flow path as a mainflow path. In its case, the pretreatment part is a dispensation partperforming at least filling of a separation buffer solution andinjection of a sample into each of the electrophoretic flow paths, theprocessing part includes an electrophoresis high voltage power supplypart capable of applying a migration voltage to each of theelectrophoretic flow paths independently of the others and a detectionpart detecting components of a sample separated in each electrophoreticflow path, and the control part controls an operation in thedispensation part so that when a pretreatment step in oneelectrophoretic flow path ends, the process proceeds to a pretreatmentstep in the next electrophoretic flow path and further controls anoperation in the electrophoresis high voltage power supply part so thata migration voltage is applied across an electrophoretic flow path inwhich a pretreatment step has ended to thereby cause electrophoresis.

In a case where the microchip processing apparatus is realized as amicrochip liquid chromatograph, each of the microchips is provided witha liquid feed flow path including a separation column as a main flowpath and performs liquid chromatography in which an analysis proceeds ina way that a sample introduced at one end of each of the separationcolumns is moved in a direction toward the other end thereof to therebyseparate the sample into components thereof and to detect thecomponents. In its case, the pretreatment part is a dispensation part atleast performing injection of the sample into each of the separationcolumns, the processing part includes a mobile phase feed mechanismcapable of feeding a mobile phase into each of the separation columnsindependently of the others and the detection part detects components ofthe sample separated in each of the separation columns, and the controlpart controls an operation in the dispensation part so that when apretreatment step in one separation column ends, the process proceeds toa pretreatment step in the next separation column and further controlsan operation in the mobile phase feed mechanism so that a mobile phaseis fed for separation in an separation column which a pretreatment stephas ended.

In the microchip processing apparatuses, the detection part may be anoptical detection part or an electrochemical detection part. The opticaldetection part may be a fluorometric measurement apparatus measuringfluorescence emitted from a sample by irradiating a part of the mainflow path with excitation light, absorption photometer measuring anabsorbance of measurement light by passing the light through a part ofthe main flow path, or an instrument measuring chemiluminescence orbioluminescence from a part of the main flow path.

Since, in a method of the invention, an analysis such as electrophoresisor a liquid chromatography can be performed in multiple flow pathssimultaneously with each other, a throughput is raised as compared withserial processing in a way such that after a pretreatment and ananalysis are performed in one flow path, a pretreatment and an analysisare performed in the next flow path.

In a case where the invention is applied to electrophoretic separation,since filling of a separation buffer solution is performed by adispenser, a separation buffer solution suitable for a sample can beselected from a number of separation buffer solutions.

Since application of a migration voltage can be set at each of theelectrophoretic flow paths independently of the others, conditions forelectrophoresis separation can be set to each sample.

In a case where the invention is applied to liquid chromatography, aneffect is obtained that a kind of an effluent, which is a mobile phase,and conditions for liquid feeding of the mobile phase can be selectedfor each sample.

Since the invention is not performed in batch processing, no wasteoccurs to any number of samples.

The foregoing and other objects, features, aspects and advantages of thepresent invention will become more apparent from the following detaileddescription of the present invention when taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a block diagram schematically illustrating a part concerning acontrol part in an embodiment in which the invention is applied to amicrochip electrophoretic apparatus.

FIG. 2 is a perspective view schematically illustrating main parts ofthe embodiment.

FIGS. 3(A) and 3(B) are plan views illustrating transparent sheet-likemembers constituting an example of a microchip and FIG. 3(C) is a frontview of the microchip.

FIG. 4 is a plan view illustrating a microchip used in the embodiment

FIG. 5 is a sectional view schematically illustrating a state ofconnection between an air feed port in a buffer filling and dischargingpart and a microchip in the embodiment.

FIGS. 6(A) and 6(B) are time charts illustrating operations in theembodiment.

DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 1 is a block diagram schematically illustrating a part concerning acontrol part in an embodiment in which the invention is applied to amicrochip electrophoretic apparatus.

A numerical symbol 2 denotes a dispenser, which sucks a separationbuffer solution and a sample separately to inject them into one end ofan electrophoretic flow path in a microchip by a syringe pump 4, and thedispenser 2 is commonly provided to multiple electrophoretic flow paths.A numerical symbol 16 denotes a separation buffer filling anddischarging part by means of which each of the eletrophoretic flow pathsis filled with a separation buffer solution injected into one end of theelectrophoretic flow path by air pressure and unnecessary separationbuffer solution is discharged with a suction pump part 23. Theseparation buffer filling and discharging part 16 is also commonlyprovided to the multiple electrophoretic flow paths in which processingis to be performed. A numerical symbol 26 denotes an electrophoretichigh voltage power supply part applying a migration voltage to each ofthe electrophoretic flow paths independently of the others. A numericalsymbol 31 denotes a fluorometric measurement part as an example ofdetection part detecting components of a sample separated in each of theelectrophoretic flow paths.

A numerical symbol 38 denotes a control part, which controls anoperation in the dispenser 2 so that when filling of a separation buffersolution and injection of a sample into one electrophoretic flow pathends, the process proceeds to filling of a separation buffer solutionand injection of a sample into the next electrophoretic flow path,further controls an operation in the electrophoretic high voltage powersupply part 26 so that a migration voltage is applied to anelectrophoretic flow path which injection of a sample has ended tothereby cause electrophoresis therein, and still further controls adetecting operation by the fluorometric measurement part 31.

A numerical symbol 40 denotes a personal computer as an external controlapparatus for commanding an operation in the microchip electrophoreticapparatus and capturing and processing data obtained by the fluorometricmeasurement part 31.

FIG. 2 schematically illustrates main parts of the microchipelectrophoretic apparatus of an embodiment. Four microchips 5-1 to 5-4are held on a holding part 11. Each of the microchips 5-1 to 5-4, asdescribed later, has one electrophoretic flow path formed for processingone sample.

The dispenser 2 for dispensing separation buffer solutions and samplesto the microchips 5-1 to 5-4 is provided with a syringe pump 4performing suction and discharge, a probe 8 having a dispensing nozzle,and a container 10 for a cleaning liquid, wherein the probe 8 and thecontainer 10 are connected to the syringe pump 4 by way of a three-wayelectromagnetic valve 6. The separation buffer solutions and the samplesare contained in respective wells on a micro-titer plate 12, and thesamples and the separation buffer solutions are dispensed to themicrochips 5-1 to 5-4 by the dispenser 2. Note that the separationbuffer solutions may be placed in the vicinity of the micro-titer plate12 being contained in the respective containers. A numerical symbol 14denotes a cleaning part for cleaning the probe 8, which overflows with acleaning liquid.

The dispenser 2 is of a construction in which the three-wayelectromagnetic valve 6 is connected in a direction in which the probe 8and the syringe pump 4 are connected to each other to suck a separationbuffer solution or a sample from the probe 8 with the syringe pump 4 andto discharge the separation buffer solution and the sample into one ofthe electrophoretic flow paths in the microchips 5-1 to 5-4 with thesyringe pump 4. When the probe 8 is cleaned, the three-wayelectromagnetic valve 6 is changed over in a direction in which thesyringe pump 4 and the container 10 for a cleaning liquid are connectedto each other, and the cleaning liquid is sucked into the syringe pump4. Thereafter the probe 8 is dipped into the cleaning liquid of thecleaning part 14, and the three-way electromagnetic valve 6 is changedover to the side where the syringe pump 4 and the probe 8 are connectedto each other to discharge the cleaning liquid from inside of the probe8, thereby performing cleaning.

In order for the electrophoretic flow path to be filled with aseparation buffer solution dispensed into a reservoir at one end of theelectrophoretic flow path of each of the microchips 5-1 to 5-4, a bufferfilling and discharging unit 16 is commonly provided to the fourmicrochips 5-1 to 5-4. An air discharge port 18 of the buffer fillingand discharging unit 16 is pressed against the reservoir at the one endof the electrophoretic flow path of the one of the microchips 5-1 to 5-4with air-tightness and suction nozzles 22 are inserted into the otherreservoirs of the electrophoretic flow path. Air is blown from the airdischarge port 18 to push the separation buffer solution into theelectrophoretic flow path while sucking the separation buffer solutionwhich overflows from the other reservoirs with the nozzles 22 by asuction pump to discharge the overflowed solution to outside.

In order to apply a migration voltage to each of the electrophoreticflow paths of the microchips 5-1 to 5-4 independently of the others, anelectrophoresis high voltage power supply 26 (26-1 to 26-4) is providedto each of the microchips 5-1 to 5-4 independently of the others.

The fluorometric measurement parts 31 provided to the respectivemicrochips, each of which detects components of a sampleelectrophoretically separated in the separation flow path 55 of acorresponding one of the microchips 5-1 to 5-4, have LEDs (lightemitting diodes) 30-1 to 30-4 for irradiating parts of the respectiveelectrophoretic flow paths with excitation light, optical fibers 32-1 to32-4 for receiving fluorescence emitted from the sample components whichmove in the electrophoretic flow paths and are excited by the excitationlight from the LEDs 30-1 to 30-4, and an photomultiplier 36 receivingfluorescence through a filter 34 that removes an excitation lightcomponent from the fluorescence transmitted by the optical fibers 32-1to 32-4 to transmit only fluorescence components. Each of the LEDs 30-1to 30-4 is light-emitted while staggering light emitting thereof fromthe others, thereby enabling four kinds of fluorescence to be identifiedand detected with the one photomultifier 36. Note that an LD (laserdiode) may be used as a light source for excitation light without beinglimited to an LED.

FIGS. 3A to 3C and FIG. 4 illustrate an example of a microchip of theembodiment. A microchip in the invention means such an electrophoreticapparatus in which an electrophoretic flow path is formed in asubstrate, wherein the apparatus is not necessarily limited to a smallone in size.

A microchip 5 is, as illustrated in FIGS. 3A to 3C, constituted of apair of transparent substrates (substrates made of a quartz glass orother kinds of glass, or resin substrates) 51 and 52. Electrophoreticcapillary grooves 54 and 55 intersecting with each other are, asillustrated in FIG. 3B, formed on a surface of one substrate 52, andreservoirs 53 are, as illustrated in FIG. 3C, formed as through holes atpositions corresponding to ends of the grooves 54 and 55 in the othersubstrate 51. Both substrates 51 and 52 are, as illustrated in FIG. 3C,superimposed on one another and adhered to each other to form anelectrophoretic separation flow path 55 and a sample introducing flowpath 54 for introducing a sample into the separation flow path using thecapillary grooves 54 and 55.

A microchip 5 is basically one illustrated in FIG. 3A to 3C and for thesake of easy handling, as illustrated in FIG. 4, the microchip 5 onwhich electrode terminals for applying a voltage are formed in advanceon the chip is employed. FIG. 4 illustrates a plan view of the microchip5. The reservoirs 53 also work as ports to which a voltage is appliedacross the flow paths 54 and 55. Ports #1 and #2 are ports located atboth respective ends of the sample introducing flow path 54 and ports #3and #4 are ports located at both respective ends of the separation flowpath 55. In order to apply a voltage to each port, electrode patternswith FIGS. 61 to 64 formed on the surface of microchip 5 are formedextending to the side ends of the microchip 5 from the ports, which areconnected to the respective electrophoresis high voltage power supplies26-1 to 26-4.

FIG. 5 schematically illustrates a state of connection between an airfeed port 18 in the buffer filling and discharging part 16 and themicrochip 5. An O ring 20 is provided at the distal end of the air feedport 18 and the air feed port 18 is pressed against one reservoir of themicrochip 5, and the air feed port 18 can thereby be mounted onto theelectrophoretic flow path of the microchip 5 with air-tightness, therebyenabling pressurized air to be fed into the flow path from the air feedport 18. The nozzles 22 are inserted to the other reservoirs and theunnecessary separation buffer solution overflowing flow paths is suckedand discharged.

FIGS. 6A and 6B illustrate operations in an embodiment in a detailedmanner. In the operations, a case is adopted where one electrophoreticflow path is formed on one microchip. Therefore, that the processproceeds from one microchip to the next microchip is the same in meaningas that the process proceeds from one electrophoretic flow path to thenext eletrophoretic flow path.

FIG. 6A illustrates operations in the embodiment in which thepretreatment step and an electrophoresis and light measurement step aresequentially performed on four microchips while operating partlysimultaneously with each other.

The steps are set in time; 40 sec are spent in the pretreatment step and120 sec are spent in the electrophoresis and light measurement step. Onecycle per microchip is 160 sec.

When a pretreatment step on one microchip ends, the process proceeds toa pretreatment on the next microchip without waiting for completion ofthe electrophoresis and light measurement step on the former microchip.That is, when the pretreatment step on the first microchip ends, apretreatment step on the second microchip starts while anelectrophoresis and light measurement step starts on the firstmicrochip. When the pretreatment step on the second microchip ends, apretreatment step on the third microchip starts while an electrophoresisand light measurement step starts on the second microchip. In such away, the pretreatment step is repeated on microchips on a one on onebasis, while separately from operations concerning pretreatment steps,the electrophoresis and light measurement step sequentially starts on amicrochip on which a pretreatment has ended, with the result that theelectrophoresis and light measurement steps are performed on multiplemicrochips simultaneously to each other. When the pretreatment step hasbeen performed on a fourth microchip, similar processing is repeated onthe first microchip in the second use thereof since an analysis has beencompleted on the first microchip.

In the electrophoresis step, a voltage is applied in order to guide asample up to an intersection of the sample introducing flow path and theseparation flow path from the sample introducing flow path andsubsequent to this, separation by electrophoresis due to application ofa voltage in the separation flow path is performed. In company withthis, irradiation with light from LED is performed at a detectionposition and fluorometric measurement starts.

The pretreatment step is illustrated in FIG. 6B in a detailed manner.

Numerical values at the uppermost level indicate times in sec. A lateralspace with a title of “Microchip” illustrates contents of processing onone microchip. A lateral space with a title of “Dispensation part”illustrates operations of suction and discharge of a separation buffersolution and a sample through the probe 8 performed by the syringe pump4. A lateral space with a title of “Syringe pump” illustrates operationsof the syringe pump 4. A lateral space with a title of “Separationbuffer filling and discharging part” illustrates filling operationspushing a separation buffer solution dispensed onto a microchip into aflow path and operations performed by a suction pump in a suction stepsucking and discharging the overflowing separation buffer solution, anda lateral space with a title of “Suction pump” illustrates operations ofthe suction pump for the separation buffer filling and discharging part16. Lateral spaces with a title of “Electrophoresis high voltage powersupply part” and with a title of “Fluorometric measurement part”illustrate operations of the respective parts.

In the lateral spaces, “B” means a buffer solution; “Suct” and “S” inthe lateral space with the title of “Syringe pump” mean suction; “Fill.& Suct” means “filling and suction”; “W1 to W4” means the number ofreservoirs; “D” and “dis” mean dispensation; and “S” in “W1S” means asample.

In the lateral space with the title of “microchip”, a first suction ofseparation buffer solution (“B suct”) is a step of sucking anddischarging a separation buffer solution having been used in thepreceding analysis. In the next step (“W4B”) step, a separation buffersolution is dispensed into a fourth reservoir. In the next step (“Fill.& Suct.”), pressurized air is fed from the separation buffer filling anddischarging part to push the separation buffer solution into a flow pathwhile sucking and discharging the unnecessary separation buffer solutionfrom the other reservoirs, thereby cleaning the flow path with the newseparation buffer solution.

In order to clean a first reservoir in the next step (“W1B”), aseparation buffer solution is newly dispensed into the first reservoir,and pressurized air is supplied to the fourth reservoir from theseparation buffer filling and discharging part in the next step (“Fill.& Suct”) to push the separation buffer solution of the fourth reservoirinto the flow path to cause the flow path to be filled with theseparation buffer solution while sucking and discharging the unnecessaryseparation buffer solution from the other reservoirs. Thereafter, theseparation buffer solution is dispensed from second, third and fourthreservoirs in the next step (“W2, 3, 4 B dis.)”. Thereby, filling of theseparation buffer solution into the flow paths is completed.

Subsequently, a sample is sucked into the probe in the dispensation partfor dispensing the sample and the sample is discharged into the firstreservoir in a step (“W1S”) for dispensation of the sample. The probe ofthe dispensation part is cleaned after dispensation of the sample andthereafter, the probe waits for suction of a separation buffer solutionfor the next sample. With all the steps performed, the pretreatment stepfor the flow paths in the microchip ends.

While in each of the microchips of the embodiment, a flow path of across injection scheme is adopted, no specific limitation is placedthereon and microchips each having a flow path constituted of only aseparation flow path may be adopted.

While in the microchips of the embodiment, only one flow path isprovided on one microchip, multiple flow paths may be formed on onemicrochip, in which case the invention has only to be applied to eachflow path as a unit.

While in the embodiment, measurement of fluorescence is adopted in thedetection part, in addition to the fluorescence measurement, thefollowing detection methods can be adopted: measurement of absorbanceand measurement of chemiluminescence or bioluminescence.

A detection part may be of a scheme in which a light measurement systemcommonly used for all the microchips is provided, which is not of ascheme in which each of the microchips is irradiated with excitationlight independently of the others, and in the light measurement system,scanning with an optical system thereof is performed while being movedbetween detecting positions of all the microchips.

Although the present invention has been described and illustrated indetail, it is clearly understood that the same is by way of illustrationand example only and is not to be taken by way of limitation, the spiritand scope of the present invention being limited only by the terms ofthe appended claims.

1. A processing apparatus for microchips, each at least having a mainflow path performing migration of a sample for analysis inside asheet-like member, comprising: a holding part holding microchips so thatthe multiple main flow paths are provided; a pretreatment part common tothe multiple main flow paths for performing a pretreatment step prior toan analysis step in each of the multiple main flow paths; processingparts for respectively performing analysis in each of the main flowpaths independently of the others; and a control part controlling anoperation in the pretreatment part so that when a pretreatment step forone main flow path ends, a pretreatment step for a next main flow pathstarts, and further controlling an operation in the processing parts sothat an analysis is subsequently performed for the main flow path wherethe pretreatment step has ended, wherein each of the microchips has anelectrophoretic flow path including a separation flow path as the mainflow path, wherein the pretreatment part includes a dispensation partperforming at least filling of a separation buffer solution andinjection of a sample into each of the main flow paths, wherein each ofthe processing parts includes: an electrophoresis high voltage powersupply capable of applying a migration voltage to each of the main flowpaths independently of the others; and a detection part detectingcomponents of the sample separated in each of the main flow paths, andwherein the control part controls an operation in the dispensation part,and further controls an operation in the electrophoresis high voltagepower supply so that the migration voltage is applied across the mainflow path which the pretreatment step has ended to thereby causeelectrophoresis, wherein the electrophoresis high voltage power supplyis provided to each of the main flow paths independently of the others,and wherein the control part controls the operations in the dispensationpart and in the electrophoresis high voltage power supply so that theelectrophoresis of the main flow path is performed independently of theother main flow paths and simultaneously with a pretreatment step forthe next main flow path, thereby the electrophoresis of the main flowpaths are performed simultaneously with different start time to oneanother among the main flow paths.
 2. The processing apparatus accordingto claim 1, wherein the detection part is a fluorometric measurementapparatus measuring fluorescence.